JPH0248262B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to an iontophoresis guide and its device, and particularly to an extremely easy-to-operate and lightweight iontophoresis guide or plaster structure that can be directly attached to human skin. Ionophore has recently been attracting increasing attention as an effective topical administration method that promotes transdermal absorption of ionic drugs (Glass JM et al., Int.J.
Dermatol.19 519 (1980); Russo J., Am.J.
Hosp.Pharm.37 843 (1980); Gangarosa LP et
al., J.Pharmacol.Exp.Ther.212 377 (1980);
Kwon BS et al., J.Infect.Dis.140 1014
(1979); Hill JM et al., Ann.NY.Acad.Sci.284
604 (1977) and Tannebaum M.Phys.Ther.60
792 (1980), etc.). The ionophoreses in these prior art are
Normally, the output terminal of a continuous current generator or an intermittent current generator is connected to a conductor made of a conductor such as a metal plate covered with absorbent cotton impregnated with a chemical solution or an independent conductor of similar construction. Therefore, its implementation is quite complicated, and although it is an extremely effective medication method, its widespread use has been limited. In addition, these conductors are generally fixed to the treatment area with rubber bands, etc. to apply transdermal electricity, so burns are likely to occur due to poor contact between the skin and the conductor, so constant contact with the conductor is required during the treatment. Since it required monitoring with an ammeter, there was no hope that it would become popular as a general home treatment, even if it was only used by doctors. Therefore, the main object of the present invention is to overcome the difficulties of these known techniques and to provide a novel iontophoresis conductor or plaster structure that is extremely easy to operate and lightweight and can be directly attached to human skin. . First, the conductor structure of the present invention will be explained in detail based on one embodiment shown in the attached FIGS. 1 and 2. In the figure, the conductor 2 is an ionic chemical solution or electrolyte solution made of water-absorbing paper materials, cloth materials such as gauze, fiber materials such as absorbent cotton, sponges or porous materials such as open synthetic resin foams or water-absorbing resins. A water-absorbing member 4 for impregnation retention, a conductive member layer 5 for current dispersion made of a metal foil such as aluminum foil, a conductive rubber or resin film, a film deposited with a conductive substance, etc., formed around the water-absorbing member 4. It consists of a hydrophilic adhesive or gel layer 11 having a skin adhesive property and a backing layer 10 such as a synthetic resin film integrally laminated thereon. Here, the conductive member layer 5 may be a backing layer formed by vapor-depositing metal such as aluminum, and appropriate terminals may be provided as required. Furthermore, a barrier layer 12 made of a synthetic resin material or the like may be provided between the hydrophilic gel layer 4 and the water-absorbing member 4 to prevent penetration of a chemical solution or the like into the gel. The conductor of the present invention having the above structure is obtained by impregnating the water-absorbing member 4 with an ionic chemical solution, or placing and inserting the member pre-impregnated with the drug solution in a predetermined position, and directly contacting and adhering it to the skin. put into use. Therefore, during use, since the drug solution holding part is surrounded by a skin-adhesive and hydrophilic gel layer, the appropriate water absorbency of the gel layer effectively prevents the drug solution from escaping and leaking onto the skin. The skin adhesion ability of the conductor as a whole is not weakened, and stable current supply and accurate local administration of the medicinal solution are possible. That is, according to the conductor of the present invention, an ideal chemical solution or electrolyte storage structure is simultaneously achieved that does not require complicated fixing means such as a band, and effectively prevents the outflow of the chemical solution. Since the conductor of the present invention has the above-mentioned effect, it can be widely used by connecting its terminal to various iontophoresis devices. It can be said that the plaster structure for iontophoresis according to the present invention is particularly useful. Note that FIG. 1 is a plan view of the conductor of the present invention, and FIG. 2 is a sectional view thereof. Hereinafter, a first embodiment of the plaster structure of the present invention will be described in detail with reference to FIGS. 3 to 5 of the drawings. In the figure, reference numeral 1 denotes a plaster structure for iontophoresis, which has a separator 2 and a separator 3. The seki conductor 2 is made of paper material such as water-absorbing paper, cloth material such as gauze, fiber material such as absorbent cotton, sponge or porous material such as open synthetic resin foam or water-absorbing resin, etc. impregnated with an ionic chemical solution. Holding water absorbent member 4
, a hydrophilic gel layer 11 and a current dispersion conductive member layer 5 formed of metal foil such as aluminum foil, conductive rubber or resin film, etc. Furthermore, the insensitizer 3 includes a skin-adhesive conductive gel layer 6 formed in the form of a flexible sheet or film;
It is integrally formed by laminating the current dispersion conductive member layer 7 made of aluminum foil or the like as described above. A lightweight battery, for example, a so-called button-shaped battery 8 is installed approximately in the center of the upper surface of the conductor 2 so that one pole, for example, the (-) pole thereof, contacts the current dispersion conductive member layer 5. Further, the (+) pole of this button-shaped battery 8 is connected to the current dispersion conductive material layer 7 of the indifferent conductor 3 through a lead wire 9 made of aluminum foil, for example, whose lower surface except near both ends is coated with an insulator. has been done. 10 is an insulating backing layer. This insulating backing layer 10 is made of, for example, a non-conductive synthetic resin formed in the form of a flexible sheet or film. ing. That is, the conductor 2, the conductor 3, and the button-shaped battery 8 are integrally supported and connected by the insulating backing layer 10.
Further, in this example, an insulating synthetic resin barrier layer 12 is provided. Next, the function and usage of the plaster structure for iontophoresis of the present invention constructed as described above will be explained. First, the water-absorbing material layer 4 of the separator 2 is impregnated with a desired ionic chemical solution, and then the separator 2 is attached to a desired position on the human body so as to come into contact with it. At the same time, Seki conductor 2 and Insen conductor 3 form a closed circuit,
Penetration of the ionic chemical liquid into the water-absorbing member layer 4 for impregnation with the ionic chemical liquid of the conductor 2 is accelerated. Each component of the plaster structure of this example will be explained in more detail as follows. Skin-adhesive hydrophilic (conductive) gel layer This layer is preferably made of natural resin polysaccharides such as karaya gum, tragacanth gum, xanthan gum or partially saponified polyvinyl alcohol, polyvinyl formal, polyvinyl methyl ether and its copolymers, polyvinyl pyrrolidone, polyvinyl Vinyl resins such as methacrylate, polyacrylic acid and its sodium salt, polyacrylamide and its partially hydrolyzed products, partially saponified polyacrylic esters, poly(acrylic acid-acrylamide)
Various hydrophilic natural or synthetic resins, such as acrylic resins, are softened and plasticized with water and/or alcohols such as ethylene glycol and glycerin to produce flexible films or sheets that have self-shape retention and skin adhesion. Supplied as a gel. On the other hand, when these are conductive gel layers of unconducted conductors, electrolytes such as sodium chloride, sodium carbonate, potassium citrate, etc. are added in the required amount (usually about 1 to 15%) to provide sufficient conductivity. degree) added. The hydrophilic (conductive) gel layer suitable for the present invention obtained in this way is in the form of a flexible film or sheet and can be closely attached to the skin, so it has a low skin contact resistance and allows drug ions to pass through the skin. Not only is it effective for penetration, but it also has the advantage of being able to adhere and support the entire structure to the skin without requiring other skin adhesive means such as adhesive tape. In particular, when a natural resin polysaccharide such as the aforementioned Karaya gum is used as a base material for the gel layer, its natural polymeric acid structure provides PH buffering and skin protection properties, extremely high water retention capacity, moderate skin adhesion, etc. ,
Not only can a conductive gel with good electrochemical properties be provided, but also suitable skin compatibility can be obtained. Some preferred composition ranges (parts by weight) of karaya gum gel are shown in Tables 1 and 2 below.

[Table] Use saline solution.

[Table] ○R
*) Herkyles “Reten 521PX”
The conductor of the present invention, which is made of a hydrophilic polymer material such as those exemplified above, absorbs a small amount of drug solution at the boundary when it is applied to the skin, but its adhesiveness is further strengthened by this, so it is possible to absorb the drug solution on the skin. It constitutes a so-called chemical reservoir that is kept hermetically sealed, and it can be said to be extremely simple to use in that it does not require any fixing means such as a band. In addition, when it comes to the composition of these gel layers, it goes without saying that electrochemical considerations should be taken in the same manner as in the case of so-called electrophoretic gels, but the main consideration is that of the chemicals used. It is carried out as appropriate so that the electrical conductivity reaches the required value, depending on the type and required dosage (dose), the duration of application, the output of the battery used, the skin contact area, etc. Here, some of the other suitable hydrophilic (electroconductive) gel layers in this example are more specifically as follows: 1. An average molecular weight of 440,000 and a degree of saponification of approximately 60
Adjust 30g of polyvinyl alcohol powder,
To this, 40 g of distilled water containing 10% NaCl and 30 g of glycerin, which had been preheated to 80°C, were added and stirred.
The resulting mixture was then heated and pressed for about 20 minutes at a pressure of 0.6 kg/cm ² using a hot press heated to 80° C. to obtain a flexible sheet with a thickness of 3 mm.
This flexible sheet-like material had sufficient skin adhesion and had a specific resistance of 0.8 KΩ·cm. 2 A flexible sheet-like conductive gel layer was manufactured using the following composition in the same manner as in 1 above. Composition example A Polyvinylpyrrolidone (PVP-K90 manufactured by GAF;
Average molecular weight: 360,000)...20g Distilled water containing 10% NaCl...40g Glycerin...40g The obtained sheet had strong skin adhesion and its specific resistance was 0.2KΩ·cm. Composition example B Polyvinyl formal (average molecular weight 1.6 million, formalization degree 15%; saponification degree of raw material polyvinyl alcohol 60%) ...15g Distilled water containing 5% NaCl ...70g Probylene glycol ...15g The obtained sheet is It had sufficient skin adhesion and its specific resistance was 1.0KΩ·cm. Composition example C Polyvinyl acetoacetal (average molecular weight 440,000,
Degree of acetalization: 30%; Saponified product of starting polyvinyl alcohol: 70%) ...40g Distilled water containing 15% NaCl ...50g Ethylene glycol ...10g Has sufficient skin adhesion and has a specific resistance of 0.75KΩ.
cm. 3 Sodium polyacrylate (Nippon Pure Chemical Industries, Ltd. Aronbis SS; average molecular weight 3 million to 5 million) 20 g at 5%
12g of distilled water containing NaCl and 68g of glycerin solution
The mixture was mixed uniformly with the mixture and heated and pressed at 80°C for 10 minutes to obtain a flexible sheet. This sheet has moderate skin adhesion and its specific resistance after being left for one day and night.
It was 0.5KΩ・cm. 4 30g of Karaya gum and 30g of distilled water containing 5% NaCl
and 40 g of glycerin were mixed and heated and pressed to prepare a sheet in the same manner. Specific resistance 0.65KΩ・cm. 5 Sodium polyacrylate (Aronbis S manufactured by Nippon Pure Chemical Industries, Ltd.; average molecular weight 3 million to 5 million) 20 g 7%
A sheet was prepared in the same manner by mixing with 80 g of NaCl-containing purified water and applying heat and pressure. Specific resistance 0.47KΩ・cm. As is clear from the above, the gel base material composition or range of the hydrophilic (conductive) gel layer of the present invention is not limited to a specific one, and a wide range of hydrophilic polymers can be mixed with water and/or alcohols. Although it is used after being softened and plasticized, the composition is usually selected within the range of 10 to 70% by weight of hydrophilic polymer and the balance water and/or alcohol in order to have shape retention. Each of the above-mentioned conductive gel layers has sufficient skin adhesion by itself, but if desired, a pressure-sensitive adhesive component such as an acrylic adhesive or a vinyl acetate emulsion adhesive may be added. It's okay. The above example was explained with reference to the conductive gel layer of the Inkan doshi, but when these are used as the Kando's hydrophilic gel layer or the adhesive layer in the integrated plaster described later, the addition of electrolyte components is only necessary. Of course, that's fine. Ionic drugs All ion dissociative drugs can be used, but
Some examples of those already widely used in the ionophore field are as follows: iodopotassium, procaine hydrochloride, melicol, and vitamins.
Various skin vitamins and skin nutrients such as B ₁ , B ₂ , B ₆ , C and various amino acids, histamine, sodium salicylate, dexamethasone, epinephrine, hydrocortisone, idoxolidine, insulin, undecylenate, various antibiotics, etc. Lightweight Batteries and Outputs Any type of battery, such as a button-shaped battery or a sheet-shaped battery, can be used as long as it is lightweight and can be used by pasting current, but the above two types are usually preferably used due to their small size and flexibility. On the other hand, the current value required to perform iontophoresis is usually about several μA to several 100 μA/cm ² , and the contact resistance between the conductor and the skin is from several KΩ to several 10 KΩ.
Therefore, the output of the battery is approximately 0.5 to 18 V, depending on the contact area between the skin and the conductor. Therefore, if necessary, it is possible to use an amplifying element in which several of these lightweight batteries are arranged, or several of them are laminated or chipped. Further, if necessary, a constant current element or a light emitting element to indicate energization may be added. Water-absorbing member Any material can be used as long as it can impregnate and retain an aqueous ionic drug solution, such as water-absorbing paper, cloth,
Suitable examples include sponge materials, porous materials, and the like. Example of Use One example of the use of the structure shown in the attached FIGS. 3 to 5 will be described in more detail as follows. That is, the conductive gel layer is made of the aforementioned Karaya gum gel or sodium polyacrylate (Alonbis S) 20% by weight, distilled water containing 20% NaCl 15% by weight, and glycerin 65% by weight, and has a thickness of 1.5 mm and an area of about 24 cm ² of skin. On the other hand, the hydrophilic gel layer has the same composition as above except that it lacks NaCl, and the water absorbent layer has a thickness of about 1.7 mm and an area of about 3 cm ² (hydrophilic gel layer). It is made of gauze material or polyvinyl formal sponge material with a gel layer of 9 cm ² ). On the other hand, the conductive members 5 and 7 for current distribution use aluminum foil in this case, and connect the cathode of the button-shaped battery 8 (output voltage 3V x 2) directly to the inductor 2, and the anode to the electrode through the lead wire 9. This is connected to the conductor 3, and the entire structure is integrally laminated with a polyethylene film 10 using a heat sealing method to provide the plaster structure 1. In use, the water-absorbing member layer 4 is impregnated with 1 to several ml of an aqueous solution containing 10% vitamin C (sodium ascorbate) (stored in ampoules), and then the entire structure is attached to the affected area to begin the treatment. be done. As is well known, vitamin C (ascorbic acid) or its derivatives (sodium ascorbate, etc.)
is effective for pigmentation disorders such as so-called melasma, sparrow spots, and various types of melasma, and treatment using iontophoresis is already known to be useful in cosmetics and dermatology. However, as mentioned above, it is not widely used due to the complicated operation. However, this example allows the treatment to be performed with extremely simple operations, and can be said to be revolutionary as a therapeutic or cosmetic plaster. In addition, when using the configuration of this example on the face, the amount of current is normally 10 to 80 μA/cm ² , and vitamin C
It takes about 20 to 60 minutes for it to reach the melanocyte-containing epidermal basal cell layer. In addition, the plaster structure in this usage example is applied as an analgesic/anti-inflammatory plaster when sodium salicylate or the like is used, but in this case, the so-called galvanization method that exhibits a vasodilatory effect is also performed. Therefore, it can be understood that it shows a synergistic effect on diseases such as neuralgia, arthralgia, and rheumatoid arthritis. Other gel base materials Some preferred examples of the gel base material for the hydrophilic (conductive) gel layer or adhesive layer of the present invention are as described above, but in addition, various hydrophilic base materials known as so-called biological electrode materials, etc. It is once again pointed out that flexible polymeric materials can be selected and used at will. For example, Tokukai Akira
52-95895, 54-77489, 56-15728, 56-
36939, 56-36940, 57-115252, etc., can be used as the gel base material of the hydrophilic (conductive) gel layer of the present invention by appropriately adjusting the water content etc. It's something you get. In this way, the gel base material of the hydrophilic (conductive) gel layer of the present invention is a hydrophilic polymer that is softened and plasticized with water and/or alcohol to provide a skin-adhesive viscoelastic gel. The base material composition is not limited to a specific material, and the composition of the base material is determined in consideration of skin adhesion compatibility (and conductivity), etc. Furthermore, these gel layers can be disposable or replaced with other materials. Incidentally, a polarity switching means may be added to the structure so that the yin and yang of the conductor can be freely changed depending on the yin and yang of the effective drug ion species. Next, a second embodiment of the plaster structure for iontophoresis according to the present invention will be described in detail with reference to FIG. 6 of the drawings. In this embodiment, a sheet-shaped battery 15 is used as a lightweight battery. On one side of this sheet-like battery 15, conductive member layers 16 and 17 for current dispersion made of copper foil, carbon fiber nonwoven fabric, etc. are disposed, and one pole thereof is impregnated with an aqueous solution of an ionic drug and held therein. The water-absorbing member layer 4 is surrounded by a hydrophilic gel layer 11, and a conductive gel layer 6 is laminated on the other pole. According to the configuration of this embodiment, since the sheet-like battery is extremely thin at 0.5 mm to 2 mm, the thickness of the entire plaster structure 1 is also extremely thin, and a smart fluster structure without any convex portions can be obtained. Note that the output terminal of the sheet-like battery may be formed into a planar shape, and this output terminal may be used as each current dispersion conductive member layer. In this way, by arranging the skin-adhesive and conductive gel layer around the periphery and edges of the structure in addition to the adhesive properties of the Kando, there is no need for any other fixing means such as adhesive tape. The entire structure is securely fixed to the skin. If necessary, the water-retaining member layer may be made removable, and the member impregnated with a chemical solution may be placed at a predetermined position in the structure during use and used for treatment. It is also obvious that non-adhesive hydrogels commonly used in the field of electrophoresis, such as agar gel and gelatin gel, may be used in place of the water-absorbing member. An example of an agar water gel composition is as follows. Agar powder 4.0 parts by weight Purified water 100.0 〃 Vitamin C 5.0 〃 (Ascorbic acid: its Na salt ~ 1:1) This type of hydrogel piece may be layered on the structure in advance, or it may be laminated at the time of use as described above. It may be arranged. Furthermore, each of the above examples shows a case in which a non-conductor is provided at the periphery of the structure, but if sufficient skin adhesion is imparted to the hydrophilic gel layer of the non-conductor, the two can be separated to the left and right, making it possible for them to stick together. It may be a simple form connected by. Furthermore, in both of the above two examples, if the conductivity of the hydrophilic gel layer 11 is made relatively low or by providing the barrier 12, it is possible to connect and integrate the hydrophilic gel layer 6 without separating it from the conductive gel layer 6. good. In addition, it will be obvious that the indifferent conductor may also have the same structure as the inventive inductor. In this case, since a conductive gel is no longer required, a hydrophilic gel material (adhesive) with low conductivity is used.
It is sufficient to arrange two water-absorbing members spaced apart from each other via insulating barriers 12, 12 on one sheet, as shown in FIG. 7. That is, FIG. 7 shows an insulating barrier 12 having water-absorbing members 4, 4 on one sheet of hydrophilic gel 4,
This is an example in which two chemical reservoirs formed by 12 are arranged, and each pole of a button-shaped battery 8 is electrically connected to the conductive members 5 and 7 on both water-absorbing members. Furthermore, in this example, as the hydrophilic gel layer 11, a general hydrophilic adhesive (Japanese Patent Application Laid-Open No. 15731-1999,
54-70340, etc.) can be used as they are, and the present invention also includes these. In addition, in FIG. 7, the backing 10 other than the drug reservoir portion is made thicker to form a drug reservoir space, and the surface thereof is coated with a relatively thin layer of hydrophilic adhesive to form a gel layer 11. You can also use it as Alternatively, the insulating barrier layer 12 may be backing 1
It may be molded integrally with 0. Furthermore, the hydrophilic gel layer 11 may be formed only around the chemical reservoir, and the remaining portion may be replaced with an ordinary non-hydrophilic adhesive. Although we have described in detail an example in which both the conductors are integrally arranged close to each other, depending on the attachment site, it may be more convenient to separate the conductor and the conductor from each other.
In such a case, it is sufficient to simply electrically connect the two with lead wires and stack the lightweight batteries on either or both of them. Therefore, the term "integrally molded" or "integrally connected" as used in the present invention includes not only the case where the parts are simply arranged in the same backing but also the case where they are electrically connected. be. Furthermore, as the water-absorbing member of the present invention, gels such as the above-mentioned poly(acrylic acid-acrylamide) gel, polyvinyl alcohol gel, polyvinylpyrrolidone gel, etc., which have substantially high resistance (for example, 100 KΩ·cm or more) may be used. In this case, impregnation with the chemical solution lowers the resistance value of the gel, allowing efficient iontophoresis. Particularly in this case, since these gels have skin adhesive properties, they may be used to form a hydrophilic gel layer, and one continuous gel layer may constitute the skin contacting surface of the conductor. As is clear from the above, the conductor or plaster structure of the present invention enables iontophoresis, which is an effective drug promotion method, to be performed with a significantly simple operation, does not require complicated and large equipment, and is safe and reliable. It is highly effective in that it can be implemented in many cases.

[Brief explanation of drawings]

1 and 2 are schematic diagrams for explaining the conductor of the present invention, with FIG. 1 being a plan view thereof and FIG. 2 being a sectional view thereof. 3 to 5 show a first embodiment of the plaster structure for iontophoresis of the present invention,
FIG. 3 is a plan view thereof, FIG. 4 is a sectional view taken along the line - in FIG. 3, and FIG. 5 is a bottom view. FIG. 6 is a sectional view showing the second embodiment. FIG. 7 is a sectional view showing the third embodiment. DESCRIPTION OF SYMBOLS 1...Plaster structure for iontophoresis, 2...Seki conductor, 3...Seki conductor, 4...Water absorbent material layer for impregnation with ionic chemical solution, 5, 16... Current dispersion of Seki conductor 6... Skin-adhesive conductive gel layer, 7, 17... Conductive material layer for current dispersion of indifferent conductors, 8... Button-shaped battery (lightweight battery), 15... Sheet Type battery (lightweight battery)
and 11...hydrophilic gel layer.

Claims (1)

[Claims] 1. A water-absorbing member for impregnating an ionic chemical solution or an electrolyte solution that is brought into contact with the conductive member layer for current dispersion, and a water-absorbing member that surrounds it at least in order to seal and hold the drug solution impregnated in this member on the skin. A conductor for iontophoresis comprising a hydrophilic adhesive or gel layer having a hydrophilic adhesive having skin adhesive properties and a backing layer integrally accumulated thereon.